Reverse vaccinology 2.0: Human immunology instructs vaccine antigen design

Rappuoli, Rino; Bottomley, Matthew J.; D’Oro, Ugo; Finco, Oretta; De Gregorio, Ennio

ugh new vaccination strategies. Novel recombinant and soluble HIV-1 envelope (Env) proteins have been used as baits to identify and capture Env (gp160)-specific B cells by flow cytometry in selected HIV-infected donors (Scheid et al., 2009b; Wu et al., 2010) . Single-cell Ab cloning techniques have successfully generated hundreds of HIV-specific Abs and, among them, dozens of new extremely potent nextgeneration bNAbs (Doria-Rose and Connors, 2009; Klein et al., 2013; Burton and Mascola, 2015; Haynes, 2015) . The real challenge now is to take advantage of our understanding of the generation of bNAbs to design new immunogens able to induce the affinity maturation of B cell lineages expressing bNAbs. Essentially, this means being able to orchestrate a fine-tuned interplay between the host immune system and a tailored antigen (or antigens) that should prime the B cell precursors in an effective way (discussed further in the section A vacciny strategy targeting germline Abs).